Optimizing Pediatric HIV-1 Treatment in Infants With Prophylactic Exposure to Nevirapine, Nairobi, Kenya
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Globally, children who acquire HIV-1 increasingly do so in the context of maternal antiretroviral prophylaxis. It is important to determine whether maternal antiretroviral prophylaxis should alter infant treatment regimens. Nevirapine (NVP) is commonly used for PMTCT and is also a commonly used first-line drug for treatment of pediatric HIV-1. Approximately half of infants exposed to NVP have detectable NVP resistance early in infancy, with loss of detectable resistance over time. Thus, if an HIV-1 infected child was exposed to single-dose NVP prophylaxis, the question remains whether NVP or any NNRTI can be used effectively in therapeutic regimens. Alternative PI-based regimens are associated with heat-lability, poor palatability, cumulative toxicity, and fewer salvage options. This poses challenges for pediatric PI-based highly active antiretroviral therapy (HAART) in settings without refrigeration and limited antiretroviral repertoire. It is plausible that in older NVP-exposed infants (older than 6 months since exposure) who are genotypically NVP-susceptible, that nevirapine will be effective and useful.
We propose to study resistance in a pediatric HIV-1 clinical trial involving 100 children. Among children enrolled at between 6 and 18 months of age, we will provide real-time field-based genotypic NVP-resistance testing, and randomize 100 NVP-susceptible children to NVP-containing versus NVP-sparing HAART to compare therapeutic response, adverse events, and morbidity in the 2 arms during 2-year follow-up. Follow-up in these studies will be closely monitored by an external Data Safety and Monitoring Board (DSMB).
Condition | Intervention | Phase |
---|---|---|
HIV Infections |
Drug: AZT/3TC/NVP (zidovudine/lamivudine/nevirapine) Drug: d4T/3TC/NVP (stavudine/lamivudine/nevirapine) Drug: AZT/3TC/ABC (zidovudine/lamivudine/abacavir) Drug: d4T/3TC/ABC (stavudine/lamivudine/abacavir) Drug: ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir) Drug: ABC/ ddI or TDF / NVP or EFV (abacavir / didanosine or tenofovir / nevirapine or efavirenz) Drug: ABC/3TC/NVP (abacavir/lamivudine/nevirapine) |
Phase 3 |
Study Type: | Interventional |
Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
Official Title: | Optimizing Pediatric HIV-1 Treatment in Infants With Prophylactic Exposure to Nevirapine, Nairobi, Kenya (6-12 Month RCT) |
- Incidence of mortality will be compared in NVP-containing and NVP-sparing arms at every monthly visit following randomization [ Time Frame: Over 24 months of post-randomization follow-up ] [ Designated as safety issue: No ]
- CD4% will be compared in NVP-containing and NVP-sparing arms at every 3-monthly intervals following randomization [ Time Frame: Over 24 months of post-randomization follow-up ] [ Designated as safety issue: No ]
- Viral suppression in NVP-containing and NVP-sparing arms will be compared at 3, 6 and then every 6 monthly intervals following randomization [ Time Frame: Over 24 months of post-randomization follow-up ] [ Designated as safety issue: No ]
- Incidence of severe adverse events will be compared in NVP-containing and NVP-sparing arms at every monthly visit following randomization [ Time Frame: Over 24 months of post-randomization follow-up ] [ Designated as safety issue: Yes ]
- Correlates of toxicities will be compared in NVP-containing and NVP-sparing arms at every monthly visit following randomization [ Time Frame: Over 24 months of post-randomization follow-up ] [ Designated as safety issue: Yes ]
Enrollment: | 34 |
Study Start Date: | September 2007 |
Study Completion Date: | December 2009 |
Primary Completion Date: | May 2009 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
Experimental: NVP-containing
Infants randomized to this arm will receive nevirapine-containing HAART regimen
|
Drug: AZT/3TC/NVP (zidovudine/lamivudine/nevirapine)
First line regimen
Drug: d4T/3TC/NVP (stavudine/lamivudine/nevirapine)
First line regimen
Drug: ABC/3TC/NVP (abacavir/lamivudine/nevirapine)
First line regimen
|
Active Comparator: NVP-sparing
Infants randomized to this arm will receive nevirapine-sparing HAART
|
Drug: AZT/3TC/ABC (zidovudine/lamivudine/abacavir)
First line regimen
Drug: d4T/3TC/ABC (stavudine/lamivudine/abacavir)
First line regimen For children who have anaemia(Hb of<8g/dl), AZT will be substituted for d4T.
Drug: ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir)
Second line regimen
Drug: ABC/ ddI or TDF / NVP or EFV (abacavir / didanosine or tenofovir / nevirapine or efavirenz)
Second line regimen - Among children randomized to NVP sparing HAART, who will be initiated on a regimen containing lopinavir/ritonavir, zidovudine and lamivudine will be substituted with abacavir and didanosine or tenofovir (TDF) and lopinavir/ ritonavir will be replaced with nevirapine or efavirenz (EFV) in case of treatment failure of the LPV/r containing regimen.
|
Show Detailed Description
Ages Eligible for Study: | 6 Months to 18 Months |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 6-18 months age
- HIV-1 DNA detection with confirmation (positive on two HIV-1 DNA filter paper tests)
- Mother exposed to NVP-containing PMTCT regimen during currently ended pregnancy and/or infant received NVP-containing PMTCT regimen
- Infant susceptible to NVP (i.e. no detectable NVP resistance on genotypic testing)
- Caregiver of infant plans to reside in Nairobi for at least 3 years
- Caregiver is able to provide sufficient location information
Exclusion Criteria:
- Infant has received any prior antiretroviral therapy (expect prophylaxis for PMTCT)
- Infant has evidence of active tuberculosis
- Mother currently receiving NVP-containing HAART and breastfeeding the infant
Kenya | |
Kenyatta National Hospital, University of Nairobi | |
Nairobi, Kenya |
Principal Investigator: | Grace C John-Stewart, MD, PhD | University of Washington |
Principal Investigator: | Dalton Wamalwa, MMed, MPH | Department of Paediatrics and Child Health, Kenyatta National Hospital, University of Nairobi |
No publications provided
Responsible Party: | Grace John-Stewart, University of Washington |
ClinicalTrials.gov Identifier: | NCT00427297 History of Changes |
Other Study ID Numbers: | 30200-D, 2 RO1 HD023412-16;, 06-1886-D 02 |
Study First Received: | January 22, 2007 |
Last Updated: | March 16, 2010 |
Health Authority: | United States: Institutional Review Board |
Keywords provided by University of Washington:
HIV-1 Pediatric nevirapine |
HAART Resistance Treatment Naive |
Additional relevant MeSH terms:
HIV Infections Acquired Immunodeficiency Syndrome Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases Didanosine Zidovudine Stavudine Nevirapine |
Lamivudine Tenofovir Efavirenz Abacavir Ritonavir Lopinavir Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents |
ClinicalTrials.gov processed this record on March 14, 2013